Houston we have a problem! The epidemic of non medical use of prescription opioids Myron Yaster, MD Professor, Department of Anesthesiology myron.yaster@childrenscolorado.org Disclosure I have participated/consutled in funded ( sponsored ) research by the following pharmas Purdue (oxycodone, oxycontin, hydromorphone) Endo (oxymorphone) Since very few analgesic drugs have been studied in children, this lecture will include off label use of drugs. Objectives Describe a process of discovery and quality improvement in the delivery of medical care that can be used in your own practice Describe how we went from the undertreatment of pain to an epidemic of opioid abuse and how this affects your practice What are the alternatives? "The world is full of obvious things which nobody by any chance ever observes." Sherlock Holmes -The Hound of the Baskervilles Sir Arthur Conan Doyle It all started with an observation Anesthesia and Analgesia. 216;122(3):87-813
Number of Prescriptions 125 1 75 5 25 Total acetaminophen+codeine acetaminophen+hydrocodone hydromorphone methadone morphine MS-contin oxycodone oxycontin acetaminophen+oxycodone -2 2-6 6-12 > 12 Age in Years oxycodone liquid oxycodone tablet acetaminophen+codeine liquid acetaminophen+codeine tablet acetaminophen+hydrocodone liquid MScontin tablet Analysis of Controlled Substance Prescriptions: Summary of Results Amount Dispensed (ml or tablets) 6 5 4 3 2 1 Regardless of the opioid prescribed, providers wrote for very large quantities of drug to be dispensed -2 2-6 6-12 > 12 Age in Years Another Observation Which Led to More Questions Research Study Questions: How well is post-op pain managed? How much of the controlled substance prescription remains after 1-14 days at home? Is opioid therapy required at 1-14 days? At 6 months post-discharge? What do parents know about safe disposal of unused opioids?
Research Study Questions: Were they given instructions on how to dispose of leftover meds? Who informed them (physician, nurse, pharmacist)? Did they disposed of unused meds? Are there at-risk individuals in the home? (Adolescents and risk of NMUPO; young children and risk of accidental ingestion.) Anesthesia and Analgesia. 217;125: 213-22 Opioids Prescribed Oxycodone 89% Morphine Methadone 3% <1% Hydromorphone 8% 5 1 15 2 25 3 35 Number of Prescriptions Number of Respondents 16 14 12 1 8 6 4 2 n = 148 47% Parental perception of pain management n = 131 42% n = 29 9% 2% n = 5 Excellent Good Fair Poor Amount (tablet or ml) 4 3 2 1 Liquid dispensed Liquid remaining Tablets dispensed Tablets remaining All - 1 2-5 6-11 > = 12 Age (years) Doses 12 1 8 6 4 2 Doses Dispensed Doses Remaining All - 1 2-5 6-11 > = 12 52% 57% 55% 52% 51% left left left left left Age (years)
Parental perception of quantity dispensed 7 6 Too much Just right Too little 5 Percent 4 3 2 1 All - 1 2-5 6-11 12+ age in years 1 8 Disposition of "left over" opioid n = 223 96% n = 19 82% Percent 6 4 YES NO 2 n = 42 18% Told how to dispose n = 9 4% Actually disposed Storage and Disposal of Morphine at the End of Treatment Storage, n (%) Room Kitchen 115 (65) Bathroom 27 (15) Parent's bedroom 18 (1) Child's bedroom 9 (5) Other 8 (5) Open or closed space Open 76 (44) Closed 96 (56) Disposal of morphine at the end of treatment, n (%) Return to pharmacy 93 (55) Throw away 45 (27) Keep at home 16 (9) Do not know 16 (9) Abou-Karam M, et al. Parental Report of Morphine Use at Home after Pediatric Surgery. J Pediatr 215; 167: 599-64 NMUPO and Adolescents 27% mistakenly believe that misusing and abusing prescription drugs is safer than using street drugs. 33 % say they believe it s okay to use prescription drugs that were not prescribed to me to deal with an injury, illness or physical pain. 212 Partnership Attitude Tracking Study (PATS)-MetLife Foundation
Percent 1 8 6 4 2 Disposition of "left over" opioid YES NO n = 42 18% n = 19 82% Told how to dispose n = 9 4% n = 223 96% Actually disposed Opioids, Pain, and Surgery 51 million Americans undergo surgery/year For moderate to severe pain, opioids remain the gold standard for pain management Duh! 8% of patients receive opioids after surgery > 8% receive either oxycodone or hydrocodone Surgical patients routinely receive the opioids most commonly implicated in overdose deaths Pain is the 5 th vital sign Haven t we seen this before? Opioidphobia
We need DATA! Type of surgical procedure Preoperative patient characteristics Age Gender Race Language Prior opioid or alcohol use/abuse Preoperative medication use (antidepressants, benzodiazepines) Strategies to limit opioid use after surgery The Usual Suspects PK it s not just for exams Regional and Neuraxial Anesthesia Multimodal analgesia Acetaminophen NSAIDs Gabapentenoids Non pharmacologic approaches Acetaminophen AND Ibuprofen https://www.nytimes. com/218/1/27/opini on/sunday/surgerygermanyvicodin.html
Copyright 218 International Anesthesia Research Society 37 Myron Yaster, MD Basic/Translational Development of Forthcoming Opioid- and Nonopioid- Targeted Pain Therapeutics Knezevic, Nebojsa Nick; Yekkirala, Ajay; Yaksh, Tony L. Anesthesia & Analgesia125(5):1714-1732, November 217. Current and Future Targets NMDA Receptor Blockade Ketamine, Methadone, Dextromethorphan Opioid Receptor Mu, Kappa, Delta, Neuropeptide nociception Peripherally active agonists Biased ligands Alpha 2 agonists Clonidine, Tizanidine, Dexmedetomine Peripherally restricted opioids Reduced side effect profile and minimum abuse and drug seeking behavior Kappa peripherally restricted agonists are in phase 2 and 3 trials and are effective for acute, chronic, inflammatory and visceral pain as well as pruritus Biased Ligand Opioids Combine a classic mu agonist with a beta arrestin molecule modulating opioid side effects. Specifically reducing: Tolerance Respiratory depression Pruritus In phase 2 trials Cannabinoids Cannabinoid receptors (CB1 and CB2) are G protein coupled receptors (like opioids). CB1 receptors are in spinal cord neurons, particularly dorsal root ganglia CB2 are in spinal cord microglia Psychotropic and abuse potential effects are CB1, analgesia are CB1 and CB2 Cannabinoids There is NO postoperative data There is A LOT of anectodal data, particularly for opioid substitution There is evidence that it may be effective in neuropathic pain We NEED data but there are enourmous hurdles in studying a Class 1 drug
Conclusions Future Directions Need to identify reasons for overprescribing of these meds and mitigate risk to patient by behavior change and data-driven practices Develop new methods of disposal BUT We can t forget the need for humane pain management which for moderate to severe pain almost always requires opioids A Journey of Discovery Houston we have a problem! The epidemic of non medical use of prescription opioids Myron Yaster, MD Professor, Department of Anesthesiology myron.yaster@childrenscolorado.org